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Neurocritical Care
Copyright © 2005 Humana Press Inc.
All rights of any nature whatsoever are reserved.
ISSN 1541-6933/05/3:157–160
DOI: 10.1385/Neurocrit. Care 2005;3:157–160

Practical Pearl

Brainstem Infarcts as an Early Manifestation of Streptococcus

anginosus Meningitis
Sung B. Lee,1,* Lyell K. Jones,1 and Caterina Giannini2
1Departments of Neurology and 2Anatomic Pathology, Mayo Clinic College of Medicine, Rochester, MN

Abstract
Background and Purpose: Vasculitis and infarcts are well-established sequelae of bacter-
ial meningitis. However, early large-vessel involvement is rare, particularly within the
brainstem. There has been one previous case report of a young male who presented with
pontine infarct as an early manifestation of Streptococcus milleri meningitis. We present
another case of brainstem infarction associated with meningitis caused by Streptococcus
anginosus (previously referred to as S. milleri group).
Case Description: We report a 58-year-old man who developed constitutional symptoms
and gait instability, followed by progressive stupor. On examination, he had a Glasgow
Coma Scale of 8 with intact brainstem reflexes and no focal findings. Magnetic resonance
imaging documented bilateral pontine infarcts. S. anginosus was isolated from cerebrospinal
fluid. Despite proper antibiotic treatment, the patient remained comatose and care was
withdrawn. Postmortem examination revealed the meningitis was predominantly local-
ized at the base of the brain. In addition, ventriculitis, multiple abscesses, and multiple
infarcts in the pons and midbrain were found.
Conclusion: S. anginosus, which is part of the normal human flora, causes invasive pyo-
genic infections and is an uncommon cause of bacterial meningitis. This type of infection
is mostly situated at the base of the brain and has a propensity to encase the basilar artery
and its perforators, thus causing brainstem stroke early in its course.
Key Words: Streptococcus anginosus; brainstem infarct; meningitis; magnetic resonance
imaging; S. milleri.

(Neurocrit. Care 2005;3:157–160)

*Correspondence and reprint
requests to:
Sung Bae Lee
Department of Neurology,
Mayo Clinic College of
Medicine,
200 First St. SW,
Rochester, MN 55905.
E-mail: lee.sung@mayo.edu
Humana Press
Introduction
Vascular complications have been increas-
ingly recognized after streptococcal menin-
gitis (1). However, brainstem stroke is an
uncommon sequelae of bacterial meningitis.
One previous case report of a young male
presenting with a pontine infarct as an early
manifestation of Streptococcus milleri menin-
gitis suggested species proclivity (2). We
present another case of brainstem infarc-
tion associated with meningitis caused by
Streptococcus anginosus, which has previously
been referred to as S. milleri group. We discuss
the unique characteristics of S. anginosus that
may promote not only pyogenic infections but
also vasculopathy of large vessels.
Case Report
This patient was a 58-year-old, right-
handed white male who was first admitted
to an outside medical center for decreased
responsiveness and was then transferred to
the Mayo Clinic that same day. The patient
had a past medical history significant for

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Fig. 1. Magnetic resonance imaging of the brain,T1 gadolinium enhanced and fluid-attenuated inversion-recovery imaging showing abscess in the
right periventricular white matter.
hypertension and a total left hip arthroplasty 2 months before
admission. A few weeks after the hip arthroplasty, the patient
developed intermittent constitutional symptoms, including
decreased appetite and a “funny taste in the mouth.” The
patient was evaluated by his primary care physician, who at
that time only noted an enlarged liver. This finding was fur-
ther evaluated with an abdominal computed tomography (CT),
which revealed a liver mass. A biopsy of the mass showed
myofibroblastic proliferation with acute and chronic inflam-
mation. The differential diagnosis by the outside physicians
included an organizing abscess cavity versus an inflammatory
pseudotumor. However, his status rapidly declined, as exhi-
bited by worsening constitutional symptoms of fever, chills,
low-grade headache, and decreased appetite. Two days before
admission, the patient’s wife noted significant change in gait
with a clinical description most consistent with ataxia. On the
morning of admission, he awoke confused and incoherent and
became stuporous.
On arrival, the patient was febrile at 38.3ºC and had a
Glasgow Coma Scale of 8. He opened his eyes only to painful
stimuli, to which he withdrew all extremities. His speech was
reduced to incomprehensible sounds. The patient had a pos-
itive Brudzinski sign. The patient was intubated for airway
protection. Cranial nerve examination revealed 4-mm pupils
that were equal and symmetric, but pupillary responses were
sluggish. Corneal reflex and vestibulo-ocular reflex were intact
bilaterally. Gag reflex was reduced. As mentioned, the motor-
sensory exam revealed withdrawal of all extremities to painful
stimuli. Reflexes were brisk in the upper extremities and nor-
mal in the lower extremities. Toes were extensor bilaterally. In
addition, the left thigh was notable for a fluctuant mass at the
previous arthroplasty site.
Initial laboratory studies revealed a hemoglobin of 10.5
g/dL (normal 13.5–17.5 g/dL), leukocyte count of 13.2 × 109/L
(normal 3.5–10.5 × 109/L), platelet count of 653 × 109/L (nor-
mal 150–450 × 109/L), international normalized ratio of 1.3
(normal 0.8–1.2), and activated partial thromboplastin time of
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22 seconds (normal 26–38 seconds). Cerebrospinal fluid (CSF)
analysis revealed glucose <20 (normal 50–80), protein 292
(normal <45), total nucleated cells of 7676 (96% neutrophils,
4% monocytes), red blood cell count of 8282, and positive
xanthochromia. CSF and blood cultures became positive for
S. anginosus within days. Electrolytes were within normal limits.
Initial CT scan of the head showed moderate dilatation of
the temporal horns and lateral ventricles, suggestive of a com-
municating hydrocephalus. A magnetic resonance imaging
(MRI) scan of the head revealed a collection of pus in both the
right frontal horn and occipital horns. The frontal horns and
third ventricle exhibited ependymal enhancement, which was
consistent with ventriculitis. Two small abscesses within the
periventricular deep white matter bilaterally also were noted
(Figure 1). Bilateral areas of increased T2 signal intensity were
observed in the lateral pons with restricted diffusion, consis-
tent with infarcts (Figure 2). A CT scan of the abdomen and
pelvis revealed a fluid collection, which measured approxi-
mately 8 × 8 cm in the subcutaneus soft tissues and the gluteal
muscles overlying the left total hip arthroplasty. There was a
poorly defined, somewhat cystic-looking mass involving
nearly the entire right hepatic lobe (Figure 3). The patient had
normal findings on transesophageal echocardiography.
The patient was treated initially with intravenous ceftri-
axone, vancomycin, metronidazole, ampicillin, and acyclovir
before culture and sensitivity results, in addition to intra-
venous dexamethasone. After culture and sensitivity results
became known, intravenous ceftriaxone alone was contin-
ued. Instrumentation from the left total hip arthroplasty was
emergently resected, and the infected hip joint was debrided
and irrigated. An extraventricular drain was placed for
increased intracranial pressure. Interventional radiology staff
placed a hepatic drain secondary to the abscess collection in
the liver,which also grew S. anginosus in culture. Yet, despite
acute intervention and medical therapy, the patient remained
in a coma. Medical care was discontinued, and the patient
expired secondary to withdrawal of support.
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Fig. 2. Magnetic resonance imaging of the brain, and fluid-attenuated inversion-recovery, diffusion-weighted imaging, and apparent diffusion
coefficient map showing bilateral pontine infarct.
Fig. 3. Computed tomography scan of the abdomen showing an abscess
in the liver.
Postmortem neurological exam revealed S. anginosus
meningitis predominately involving the base of the brain.
Subacute infarcts, ranging from 0.2 to 1 cm in diameter, were
found within the lateral portion of the pontine bases bilater-
ally (Figure 4). An additional 0.3-cm infarct in the left midbrain
was located near the medial substantia niagra. Other associ-
ated findings included ventriculitis with fibrino-purulent
exudates in the right posterior lateral ventricle and third ven-
tricle (Figure 5). Abscesses were observed above the right
internal capsule at the level of the anterior commissure and
also at the left putamen–pallidal junction (Figure 5). The basi-
lar artery was patent.
Discussion
The mechanism for ischemic stroke in bacterial meningitis
may involve vasculitis or venous and arterial thrombosis.
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However, early large-vessel involvement is rare, particularly
within the brainstem. There has been one previous case report
of a young male who presented with a pontine infarct as an early
manifestation of S. milleri meningitis. Perry et al. described a 34-
year-old man who developed S. milleri meningitis and pontine
infarction, which progressed to a subarachnoid hemorrhage
from an infected basilar aneurysm (2). The mechanism of the
pontine stroke was explained by a thrombosis in the setting of
vasculopathy secondary to the primary infection.
S. anginosus is a bacterial organism that is an uncommon cause
of bacterial meningitis. This streptococcal species, previously
referred to as the S. milleri group, is considered a normal flora of
the oral, gastrointestinal, and urogenital tract (3). The bacteria
seems to increase in predominance with age, particularly in the
oral saliva (4). Mostly associated with pyogenic infections and
also possibly with gastrointestinal cancers, S. anginosus is con-
sidered a rare cause of meningitis, except in patients who are
immunocompromised or have certain systemic diseases, such
as diabetes (4–8). In a case series in Taiwan, 9% (7/78) of all
culture-proven meningitis was identified as resulting from a
S. viridans organism, with two identified as S. anginosus (9) The
majority of these patients had comorbid conditions, including
malignancy, trauma, and diabetes. One of the seven patients
experienced an ischemic stroke associated with the infection.
The mechanism for stroke in S. anginosus meningitis has
been proposed by Perry et al. to be primarily a vasculitic process.
However, in comparison, we were unable to show histopatho-
logical evidence for vasculopathy. Nonetheless, our patient
was found at autopsy to have a predominantly basilar menin-
gitis. The location of the infection at the base of the brain leads
to a propensity for the infection to encase the basilar artery
and its perforators, thus resulting in vascular injury and brain
stem stroke early in the clinical course of the disease.
Certain pathogenic characteristics of S. anginosus point to a
vasculitic process as a primary mechanism for stroke in this
setting. The organism has a polysaccharide capsule that hinders
phagocytosis by polymorphonuclear leukocytes. As a result,
it is relatively resistant to destruction that would be expected
in an organism that forms pyogenic abscesses. Interestingly,
S. anginosus produces hydrolytic enzymes, for example,
hyaluronidase and β-glucosidase, which can alter basement
membranes. It also can bind platelet-fibrin complexes and thus
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Fig. 4. Hematoxylin & eosin stain (left) and myelin stain (right) of pons showing bilateral strokes most affecting the pontocerebellar junction.
Fig. 5. Coronal section of the brain showing pus and ventriculitis in the right lateral ventricle (left) and abscess observed above the right internal
capsule and left putamen-pallidal junction (right).
enhance platelet aggregation promoting a prothrombotic state
(10). In predisposed vessels, all these factors contribute to the
potential for vasculopathy and subsequent ischemia.
Even though S. anginosus is part of the normal flora within
the alimentary and genitourinary tracts, patients who are either
immunocompromised or elderly are at increased risk for pyo-
genic infections and also possibly basilar meningitis from this
organism. Indeed, due to the pathogenic characteristics of this
bacterial species that lead to a proinflammatory and throm-
botic state, patients who develop S. anginosus meningitis may
be at greater risk for brainstem strokes. Vasculopathy of the
basilar artery and its perforating arteries may lead to brain-
stem ischemia. It is important to note that clinical signs of
ischemia may be an early clinical manifestation of S. anginosus
basilar meningitis.
References
1. Kastenbauer S, Pfister HW. Pneumococcal meningitis in adults:
spectrum of complications and prognostic factors in a series of
87 cases. Brain 2003;126:1015–1025.
2. Perry JR, Bilbao JM, Gray T. Fatal basilar vasculopathy compli-
cating bacterial meningitis. Stroke 1992;23:1175–1178.
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3. Whiley RA, Fraser H, Hardie JM, Beighton D. Phenotypic dif-
ferentiation of Streptococcus intermedius, Streptococcus constellatus,
and Streptococcus anginosus strains within the “Streptococcus
milleri group”. J Clin Microbiol 1990;28:1497–1501.
4. Morita E, Narikiyo M, Nishimura E, et al. Molecular analysis of
age-related changes of Streptococcus anginosus group and
Streptococcus mitis in saliva. Oral Microbiol Immunol 2004;19:
386–389.
5. Bert F, Bariou-Lancelin M, Lambert-Zechovsky N. Clinical sig-
nificance of bacteremia involving the “Streptococcus milleri” group:
51 cases and review. Clin Infect Dis 1998;27:385–387.
6. Cabellos C, Viladrich PF, Corredoira J, et al. Streptococcal menin-
gitis in adult patients: current epidemiology and clinical spectrum.
Clin Infect Dis 1999;28:1104–1108.
7. Moller K, Frederiksen EH, Wandall JH, Skinhoj P. Meningitis
caused by streptococci other than Streptococcus pneumoniae: a ret-
rospective clinical study. Scand J Infect Dis 1999;31:375–381.
8. Shenep JL. Viridans-group streptococcal infections in immuno-
compromised hosts. Int J Antimicrob Agents 2000;14:129–135.
9. Chang WN, Wu JJ, Huang CR, et al. Identification of viridans
streptococcal species causing bacterial meningitis in adults in
Taiwan. Eur J Clin Microbiol Infect Dis 2002;21:393–396.
10. Wanahita A, Goldsmith EA, Musher DM, et al. Interaction between
human polymorphonuclear leukocytes and Streptococcus milleri
group bacteria. J Infect Dis 2002;185:85–90.
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